Comprehensive Structural and Substrate Specificity Classification of the Saccharomyces cerevisiae Methyltransferome

Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity

tRNA structural and functional changes induced by oxidative stress

Oxidatively damaged biomolecules impair cellular functions and contribute to the pathology of a variety of diseases. RNA is also attacked by reactive oxygen species, and oxidized RNA is increasingly recognized as an important contributor to neurodegenerative complications in humans. Recently, evidence has accumulated supporting the notion that tRNA is involved in cellular responses to various stress conditions. This review focuses on the intriguing consequences of oxidative modification of tRNA at the structural and functional level

Estabilidade articular do joelho no quadro do "joelho-flutuante" Knee joint stability in a "floating knee" condition

Neste trabalho, 22 pacientes com fraturas ipslaterais do fêmur e da tíbia ("joelho flutuante") tratados cirurgicamente foram convocados para reavaliação. Com seguimento mínimo de 4 meses, 17 pacientes compareceram e foram reavaliados através de exame físico, radiológico, escala de Lysholm e o escore de Kärlstron. As fraturas foram classificadas quanto ao grau de exposição (Gustillo e Andersen), cominuição (AO) e o "joelho-flutuante" (Fraser). Doze pacientes (70,6%) apresentaram alterações objetivas no exame físico do joelho. A instabilidade articular foi a alteração mais encontrada, presente em oito casos (47%), seguida da restrição de movimento em sete pacientes (41,2%). A instabilidade anterior foi diagnosticada em cinco casos (29,4%), sendo três associados à instabilidade em varo. A instabilidade posterior estava presente em dois pacientes (11,8%), ambos associados com instabilidade em varo. Um paciente apresentou instabilidade periférica em varo e valgo, associada à restrição importante da flexão do joelho. As presença de fraturas intra-articulares, fraturas expostas do fêmur cursaram com maior incidência de restrição do arco de movimento. Nesta casuística os resultados obtidos reforçam a necessidade da avaliação sistemática da estabilidade articular do joelho, visto que o quadro de "joelho flutuante" está freqüentemente associado à lesão cápsulo-ligamentar desta articulação.<br>In this study, 22 patients who had undergone surgical treatment for ipsilateral fractures of the femur and tibia ("floating knee") were recalled for reassessment. Seventeen patients turned up after a follow-up period of four months and were reassessed by applying the physical and radiological exams, the Lysholm's knee scale and the Karlstron score. The fractures were classified according to degree of exposure, communication and "floating knee" condition. Twelve patients (70.6%) presented with definite alterations during the physical examination of the knee. The joint instability was present in eight cases (47%) followed by restricted movement in seven patients (41.2%). Anterior instability was diagnosed in five cases (29.4%), three of them associated with varus instability. Posterior instability was observed in two patients (11.8%) and in both cases it was associated with varus instability. One patient presented with peripheral varus-valgus instability and an important knee movement restriction. Intra-articular and exposed fractures of the femur and tibia present a higher incidence of restricted arc movement. The results obtained in this study reinforce the need for the systemic assessment of knee joint stability in view of the fact that the "floating knee" condition is often associated with lesions of the knee joint capsule and ligament